Recent technical advances in our laboratory make possible studies in the beating left ventricle of the cat. To minimize cardiac motion for visualization of the microvasculature two techniques have been utilized. High frequency jet ventilation minimizes respiratory induced motion and stroboscopic illumination of the heart synchronized to the cardiac cycle makes the microvasculature appear to be stationary. Using these techniques preliminary studies with 5-hydroxytryptamine have demonstrated that vessels greater than 100 Mum constrict while vessels less than 100 Mum dilate in response to the same stimulus. This proposal will test the hypothesis that different segments of the coronary microcirculation will respond differentially to a common stimulus. This differential response to 5-hydroxytryptamine will be examined with selective 5HT1 (methysergide) and 5HT2 (ketanserin) receptor antagonists. The effects of vagal stimulation and exogenously administered acetylcholine on the distribution of vascular resistance in the left ventricular microvasculature will be compared to determine if qualitatively similar responses occur. Finally, the effect of acute transient systemic hypertension on the response of the coronary microvasculature to endothelial dependent (5-hydroxytryptamine and acetylcholine) and endothelial independent (angiotensin II and nitroglycerine) agents will be examined. These studies of the effects of humoral agents on the microcirculation may provide conceptually important information to further our understanding of the regulation of coronary vascular resistance.